Combined oral contraceptive pill (COCP) regimens that include an antiandrogen may be more beneficial for reducing hyperandrogenism due to polycystic ovary syndrome (PCOS) compared with conventional COCPs but were not recommended as a first-line treatment, according to study results published in the European Journal of Endocrinology.

As part of the 2023 update to the International Evidence-Based Guidelines on Assessment and Management of PCOS, investigators evaluated the use of different COCPs for the treatment and management of PCOS.

A systematic review and meta-analysis were conducted of studies assessing the treatment of women with PCOS via COCPs, metformin, and antiandrogens.

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Combined oral contraceptive pills were compared based on the dose of ethinyl estradiol (EE) administered, the type of estrogen used, and the different generations of progestin; COCPs were also compared against treatment with progestin alone and with EE in combination with cyproterone acetate (CPA).

A total of 19 randomized controlled trials (RCTs) were included in the analysis. Two of the included RCTs compared high-dose (30-35 μg) vs low-dose (20 μg) EE; the only common outcome was hirsutism, with no difference observed between studies.

First-generation progestin COCPs were compared against fourth-generation COCPs among 4 different studies. Fourth-generation COCPs yielded a greater decrease in dehydroepiandrosterone sulfate (mean difference [MD], 0.78 μmol/L; 95% CI, 0.29-1.27) and androstenedione (MD, 1.13 nmol/L; 95% CI, 0.64-1.62), compared with first-generation agents.

Third-generation progestin COCPs were compared against fourth-generation progestins in 5 RCTs. Treatment with fourth-generation progestins resulted in lower body mass index (BMI; MD, 1.17 kg/m2; 95% CI, 0.33-2.02) and testosterone levels (MD, 0.60 nmol/L; 95% CI, 0.13-1.07); no difference was seen in presence of hirsutism.

Among the 4 studies included in the analysis comparing COCPs vs EE/CPA, treatment with EE/CPA resulted in lower BMI vs treatment with COCPs without CPA (MD, 0.62 kg/m2; 95% CI, 0.05-1.20). Treatment with EE/CPA was also shown to improve hirsutism and free androgen index, with lower levels of total testosterone present (MD, 0.38 nmol/L; 95% CI, 0.33-0.43).

While no studies included in the analysis reported on the risk for venous thromboembolism (VTE), the study authors noted that EE/CPA was specifically not recommended as first-line treatment for COCP according to previous guidelines, due to the VTE risk profile among the general population.

Study limitations included lack of blinding and high patient drop-out rates among RCTs included in the analysis.  Additionally, different methods were used to measure biochemical hyperandrogenism among studies. Finally, only oral contraception hormonal treatments were compared, which may limit generalizability to other administrative routes.

The study authors concluded, “This is the most up-to-date evidence on the effect of different oral contraceptive pills in PCOS which along with broader evidence on the oral contraceptives, consumer preference and multidisciplinary expertise, directly informs the 2023 update of the evidence-based guidelines on assessment and treatment of PCOS.”


Forslund M, Melin J, Alesi S, et al. Different kinds of oral contraceptive pills in polycystic ovary syndrome: a systematic review and meta-analysisEur J Endocrinol. Published online July 13, 2023. doi:10.1093/ejendo/lvad082

This article originally appeared on Endocrinology Advisor